Science Tips; Three Updates from the Weizmann Institute of Science: RHAPSODY IN RED VIOLET, FIRST BLOOD CELLS, CELL ECONOMICS 101

Pigments made by beets may help boost resistance to disease and the nutrition value of crops

Color in the plant kingdom is not merely a joy to the eye. Colored pigments attract pollinating insects, they protect plants against disease, they confer health benefits, and are used in the food and drug industries. A new study conducted at the Weizmann Institute of Science, published in the Proceedings of the National Academy of Sciences, USA, has now opened the way to numerous potential uses of betalains, the highly nutritious red-violet and yellow pigments known for their antioxidant properties and commonly used as food dyes.

Betalains are made by cactus fruit, flowers such as bougainvillea, and certain edible plants – most notably, beets. They are relatively rare in nature, compared to the two other major groups of plant pigments, and until recently, their synthesis in plants was poorly understood. Prof. Asaph Aharoni of Weizmann’s Department of Plant and Environmental Sciences and Dr. Guy Polturak, then a research student, along with other team members, used two betalain-producing plants – red beet (Beta vulgaris) and four o’clock flowers (Mirabilis jalapa) – in their analysis. Using next-generation RNA sequencing and other advanced technologies, the researchers identified a previously unknown gene involved in betalain synthesis and revealed which biochemical reactions plants use to convert the amino acid tyrosine into betalains.

To test their findings, the scientists genetically engineered yeast to produce betalains. They then tackled the ultimate challenge: reproducing betalain synthesis in edible plants that do not normally make these pigments.

The success announced itself in living color. The researchers produced potatoes, tomatoes, and eggplants with red-violet flesh and skin. They also managed to control the exact location of betalain production by, for example, causing the pigment to be made only in the fruit of the tomato plant but not in the leaves or stem.

Using the same approach, the scientists caused white petunias to produce pale violet flowers, and tobacco plants to flower in hues varying from yellow to orange-pink. They were able to achieve a desired hue by causing the relevant genes to be expressed in different combinations during the course of betalain synthesis. These findings may be used to create ornamental plants with colors that can be altered on demand.

But a change in color was not the only outcome. Healthy antioxidant activity was 60 percent higher in betalain-producing tomatoes than in average ones. “Our findings may in the future be used to fortify a wide variety of crops with betalains in order to increase their nutritional value,” says Prof. Aharoni.

An additional benefit is that the researchers discovered that betalains protect plants against gray mold, Botrytis cinerea, which causes annual losses of agricultural crops worth billions of dollars. The study showed that resistance to gray mold rose by a whopping 90 percent in plants engineered to make betalains.

The scientists had produced versions of betalain that do not exist in nature. “Some of these new pigments may potentially prove more stable than the naturally occurring betalains,” says Dr. Polturak. “This can be of major significance in the food industry, which makes extensive use of betalains as natural food dyes, for example, in strawberry yogurts.”

Furthermore, the findings of the study may be used by the drug industry. When plants start manufacturing betalains, the first step is conversion of tyrosine into an intermediate product, the chemical called L-dopa. Not only is this chemical itself used as a drug, it also serves as a starting material in the manufacture of additional drugs, particularly opiates such as morphine. Plants and microbes engineered to convert tyrosine into L-dopa may therefore serve as a source of this valuable material.

The research team included Noam Grossman, Dr. Yonghui Dong, Margarita Pliner, and Dr. Ilana Rogachev of Weizmann’s Department of Plant and Environmental Sciences and Dr. Maggie Levy, Dr. David Vela-Corcia, and Adi Nudel of the Hebrew University of Jerusalem.

Prof. Asaph Aharoni’s research is supported by the John and Vera Schwartz Center for Metabolomics, which he heads; the Leona M. and Harry B. Helmsley Charitable Trust; the Foundation Adelis; the Lerner Family Plant Science Research Fund; the Monroe and Marjorie Burk Fund for Alternative Energy Studies; the Sheri and David E. Stone Fund for Microbiota Research; Dana and Yossie Hollander, Israel; the A.M.N. Fund for the Promotion of Science, Culture and Arts in Israel; and the Tom and Sondra Rykoff Family Foundation.

Prof. Aharoni is the recipient of the André Deloro Prize and the incumbent of the Peter J. Cohn Professorial Chair.

FIRST BLOOD CELLS

Videos of forming embryonic blood vessels reveal the presence of unusual cells and the unexpected role of a well-known gene in creating blood

One of the first organ systems to form and function in the embryo is the cardiovascular system: in fact, this developmental process starts so early that scientists still have many unresolved questions on the origin of the primitive heart and blood vessels. How do the first cells – the progenitors – that are destined to become part of this system participate in shaping the developed cardiovascular system?

Dr. Lyad Zamir, a former PhD student in the lab of Prof. Eldad Tzahor in the Weizmann Institute of Science’s Department of Molecular Cell Biology, developed a method to image the earliest cardiovascular progenitors and track them and their descendants through the developing embryo in real time. His movies took place in fertilized chicken eggs, in which a complex network of blood vessels forms within the yolk sac to nourish the embryo. The findings of this research were recently published in eLife.

Working in collaboration with the lab of Prof. Richard Harvey of the Victor Chang Cardiac Research Institute and the University of New South Wales, both in Australia, Prof. Tzahor and Dr. Zamir focused on a gene called Nkx2-5. This gene encodes a transcription factor, which is a regulatory protein that controls the expression of other genes involved in the development of the heart. “The new study revealed that Nkx2-5, independently of its role in the development of the heart, plays a central role in the genesis of the very first blood vessels and indeed the formation of blood,” says Prof. Tzahor.

Looking at the onset of Nkx2-5 expression, the team revealed the existence of progenitor cells called hemangioblasts. These cells give rise to both the blood and vascular progenitor cells – those that lead to the formation of blood vessels. These unique cells are created from the mesoderm – the middle layer of cells that appears in the very early developing embryo. Researchers have been hotly debating the existence of hemangioblasts and, if they do exist, their possible function.

In the chick embryo films, the researchers could see the hemangioblasts moving to create “blood islands,” which form within the primitive embryonic vessels. The researchers were surprised to observe that some of the hemangioblast cells were moving into the heart, where they formed blood stem cells. This helped make sense of other studies revealing that the early heart tube contains cells that appear to assist in generating blood cells. The researchers also identified specialized Nkx2-5-expressing cells within the lining of the newly formed aorta, where they appeared to “bud off” to produce new blood cells. Later on in development, these specialized cells move into the liver, where they give rise to the blood-forming stem cells in the fetus.

Prof. Tzahor: “Even 20 years after one of the ‘master genes’ for heart development was discovered, we have managed to write a new story about its action, showing that it works briefly at a very early stage in development in the formation of vessels and blood – before the main action takes place in the heart. We have provided solid evidence for the existence of these very early cells and their contribution to heart and vascular development.”

Because these findings reveal the early origins of at least some of the blood-forming stem cells in the embryo, they may be especially helpful in research into diseases affecting the cardiovascular system.

Prof. Eldad Tzahor’s research is supported by the Yad Abraham Research Center for Cancer Diagnostics and Therapy, which he heads; the Henry Krenter Institute for Biomedical Imaging and Genomics; the Daniel S. Shapiro Cardiovascular Research Fund; and the European Research Council.

CELL ECONOMICS 101

The lining of our intestines uses an approach known to business to quickly process food

Every time we swallow food, cells that line the intestines must step up their activity in a sudden and dramatic manner. According to a new study by Weizmann Institute of Science researchers, reported in Science, they rise to the challenge in the most economic fashion.

In business or engineering, when one has to get production underway quickly, instant decisions are made. These might involve instantly throwing all one’s resources into boosting production with existing equipment, or else first spending all those resources to equip the plant with proper machinery. The latter might seem to be a less efficient production method but it can actually, in some cases, speed things up considerably. Dr. Shalev Itzkovitz and his team in the Department of Molecular Cell Biology discovered that this is just the method adopted in the lining of the intestinal wall.

This lining is a single layer of elongated cells that come into contact with food on one narrow side, and with the bloodstream on the other. Thus, they absorb nutrients on one side and release them into the blood on the other. The scientists discovered that the two sides of the cell differ in the composition of messenger RNA, or mRNA: about 30 percent of the genes expressed in the intestines produced mRNAs that appeared either on one side of the cell or on the other. The two sides were also found to differ in the content of protein-making machines called ribosomes: the number of ribosomes on the food-facing side was double that of the bloodstream-facing side; as a result, the production of proteins on that side was much more efficient.

The scientists further discovered that whenever food enters the bowels, cells in the intestinal lining immediately respond by increasing the production of ribosomes, particularly in the food-facing part of the cell. To this end, the cell dispatches to the food-facing area large numbers of mRNAs that carry the genetic code for making ribosomes. This part of the cell then becomes an intensive production shop of sorts, generating the proteins needed for processing the food.

Dr. Itzkovitz explains: “For most of the night and day, cells in the lining of the intestines just loll around, but once food appears, they must instantly step into action. Generating new mRNA molecules from DNA in order to make new proteins would have taken the cells about half an hour. Instead, they can increase production of certain proteins within minutes by moving the mRNA molecules encoding the relevant proteins into the side of the cell that is rich with ribosomes. This strategy enables them to deal with the arrival of food in a fast and efficient manner.”

In addition to opening the door to new studies in the “economics” of cells, the findings may have medical implications, as intestinal lining plays an important role in the both absorption of nutrients and protecting the body. It may now be possible to investigate whether the failure of mRNAs to move to the proper part of the cell – or a lack of balance between mRNAs in the high- and low-production areas of the cell – may play a role in such diseases as colitis and Crohn’s disease, and possibly also in bowel cancer.

Dr. Shalev Itzkovitz’s research is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Rothschild Caesarea Foundation; the Cymerman – Jakubskind Prize; and the European Research Council

Dr. Itzkovitz is the incumbent of the Philip Harris and Gerald Ronson Career Development Chair.

# # #

The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. The Institute’s 3,800-strong scientific community engages in research addressing crucial problems in medicine and health, energy, technology, agriculture, and the environment. Outstanding young scientists from around the world pursue advanced degrees at the Weizmann Institute’s Feinberg Graduate School. The discoveries and theories of Weizmann Institute scientists have had a major impact on the wider scientific community, as well as on the quality of life of millions of people worldwide.